cyclo(Lys-Phe)

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: cyclo(Lys-Phe)
• 英文别名: (3S,6S)-3-(4-aminobutyl)-6-benzylpiperazine-2,5-dione
• 化学式: C₁₅H₂₁N₃O₂
• 分子量: 275.351
• InChiKey: MESCLBRMEHFBJF-STQMWFEESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  84.2
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-(二甲基氨基)-1H，3H-苯并[de]异苯并吡喃-1，3-二酮 、 cyclo(Lys-Phe) 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以76%的产率得到2-(4-((2S,5S)-5-benzyl-3,6-dioxopiperazin-2-yl)butyl)-6-(dimethylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione
  参考文献：
  名称：

  Cyclic Dipeptide-Guided Aggregation-Induced Emission of Naphthalimide and Its Application for the Detection of Phenolic Drugs

  摘要：

  The development of novel aggregation-induced emission-based fluorophoric systems (AIEgens) has gained prominent importance in recent years, owing to their wide range of applications. Herein, we demonstrate the design, syntheses, and molecular architectonics of cyclic dipeptide tethered naphthalimides (CDP-NIs) to evaluate their AIEgenic properties and applications. CDPs are versatile molecular auxiliaries that form robust intermolecular hydrogen bonding and are tethered to naphthalic anhydride with the ACQ (aggregation-caused quenching) feature. The introduction of a CDP auxiliary was anticipated to promote the molecular assembly of the resulting naphthalimide product to form AIE-active aggregates through intermolecular hydrogen bonding in aqueous media. The systematic photophysical studies of CDP-naphthalimide (CDP-NI) conjugates led to the identification of two AIEgenic fluorophores. The AIEgenic property of the lead candidate 4a was employed for the detection of phenolic drugs in aqueous media. In particular, modulation of the AIEgenic property of 4a offered the sensitive detection of drugs such as doxorubicin and rifampicin (LOD = 18 nM/9.7 ppb and 202 nM/164 ppb, respectively).

  DOI：

  10.1021/acs.joc.9b02580
• 作为产物：
  描述：

  (3S)-3-氨基-4-苯基丁烷-2-酮 在 哌啶 、 氯化亚砜 、 三异丙基硅烷 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 19.5h， 生成 cyclo(Lys-Phe)
  参考文献：
  名称：

  溶剂诱导的螺旋组装和手性环二肽功能化萘二酰亚胺的可逆手性切换

  摘要：

  理解各种参数在超分子自组装过程中协调优先的手性分子组织中的作用对于设计新颖的分子功能系统具有重要意义。已经制备了环状二肽（CDP）手性辅助官能化萘二酰亚胺（NCDP 1 – 6），并研究了它们的手性自组装性能。详细的光物理和圆二色性（CD）研究揭示了溶剂在这些NCDP的手性聚集中的关键作用。NCDPs 1 - 3个形式的超分子螺旋组件，并表现出显着的手性光学开关行为（中号-至P类型）取决于HFIP和DMSO的溶剂组成。浓度和固态薄膜CD研究进一步证实了溶剂组成对NCDPs的超分子手性的强大影响。已经发现，具有相反螺旋度（M和P）的超分子聚集体之间的手性切换是可逆的，并且可以通过去除溶剂和重新溶解在特定组成的溶剂混合物中的循环来实现。具有非手性或D的控制分子系统（NCDP 4 – 6）CDP辅助物中的异构体第二个氨基酸未显示手性聚集性质。氢键和π-π相互作用在NCDP组装中的重要作用已通过核

  DOI：

  10.1002/chem.201303123

文献信息

• Phenylalanine-containing cyclic dipeptides – the lowest molecular weight hydrogelators based on unmodified proteinogenic amino acids
  作者：Alexander J. Kleinsmann、Boris J. Nachtsheim

  DOI：10.1039/c3cc44110e

  日期：——

  Cyclic dipeptides (diketopiperazines - DKPs) that are based on the proteinogenic amino acid phenylalanine in combination with serine, cysteine, glutamate, histidine and lysine are described as simple and remarkable low molecular weight hydrogelators. Blends of selected DKPs show remarkable pH-dependent properties and can be applied as easy to tune materials in drug delivery.

  基于蛋白氨基酸苯丙氨酸与丝氨酸，半胱氨酸，谷氨酸，组氨酸和赖氨酸结合的环状二肽（二酮哌嗪-DKPs）被描述为简单而引人注目的低分子量水凝胶化剂。所选DKP的共混物显示出显着的pH依赖特性，可作为易于调整的材料应用于药物输送。
• Cyclic dipeptide‐based small molecules modulate zinc‐mediated liquid–liquid phase separation of tau
  作者：Madhu Ramesh、Chenikkayala Balachandra、Prayasee Baruah、Thimmaiah Govindaraju

  DOI：10.1002/psc.3465

  日期：——

  the complex LLPS phenomenon. There are limited chemical tools to modulate protein LLPS which has therapeutic potential for neurodegenerative disorders. We have rationally designed cyclic dipeptide (CDP)-based small-molecule modulators (SMMs) by integrating multiple chemical groups that offer diverse chemical interactions to modulate tau LLPS. Among them, compound 1c effectively inhibits and dissolves

  液-液相分离 (LLPS) 是一种复杂的物理化学现象，由聚合物、蛋白质和核酸等大分子之间的多价瞬态弱相互作用介导。它对细胞生理学和疾病状况（如癌症和神经退行性疾病）有影响。许多与神经退行性疾病相关的蛋白质，如 RNA 结合蛋白 FUS（FUsed in Sarcoma）、α-突触核蛋白 (α-Syn)、TAR DNA 结合蛋白 43 (TDP-43) 和 TAu 被证明会经历 LLPS。最近，导致阿尔茨海默氏病 (AD) 和其他 TAu 病的 TAu 蛋白在体外和体内相分离成凝聚物. 生物分子之间多样化的非共价相互作用决定了复杂的 LLPS 现象。调节具有神经退行性疾病治疗潜力的蛋白质 LLPS 的化学工具有限。我们通过整合多个化学基团来合理设计基于环二肽 (CDP) 的小分子调节剂 (SMM)，这些化学基团提供不同的化学相互作用来调节 TAu LLPS。其中，化合物1c有效抑制和溶解 Zn
• Piperazine-2,5-diones as TGF-beta inhibitors
  申请人：SOUTHERN RESEARCH INSTITUTE

  公开号：US11505531B2

  公开（公告）日：2022-11-22

  The present disclosure is concerned with piperazine-2,5-diones that are capable of inhibiting TGF-β and methods of treating cancers such as, for example, multiple myeloma and a hematologic malignancy, and methods of treating fibrotic conditions using these compounds. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  本公开涉及能够抑制 TGF-β 的哌嗪-2,5-二酮和治疗癌症（例如多发性骨髓瘤和血液恶性肿瘤）的方法，以及使用这些化合物治疗纤维化病症的方法。本摘要旨在作为在特定技术领域进行搜索的扫描工具，并非对本发明的限制。
• Hybrid molecules synergistically mitigate ferroptosis and amyloid-associated toxicities in Alzheimer's disease
  作者：Dikshaa Padhi、Prayasee Baruah、Madhu Ramesh、Hariharan Moorthy、Thimmaiah Govindaraju

  DOI：10.1016/j.redox.2024.103119

  日期：2024.5

  properties of gallic acid (GA) and cyclic dipeptides (CDPs) to synthesize hybrid molecules that effectively target both ferroptosis and amyloid toxicity in AD. This innovative approach marks a paradigm shift from conventional therapeutic strategies. This is the first report of a synthetic small molecule () that effectively combats ferroptosis, simultaneously restoring enzymatic activity and enhancing cellular

  阿尔茨海默病 (AD) 是一种神经退行性疾病，其特征是细胞外 β 淀粉样蛋白 (Aβ) 斑块和细胞内神经原纤维缠结 (NFT) 的形成。铁死亡是一种铁 (Fe) 依赖性细胞死亡形式，通过产生活性氧 (ROS)、线粒体损伤、脂质过氧化以及谷胱甘肽过氧化物酶 4 (GPX4) 酶活性降低，在多方面 AD 发病机制中发挥着重要作用。水平。 tau 蛋白的异常液-液相分离 (LLPS) 会促进 NFT 的生长和成熟，从而导致 AD 发病。在这项研究中，我们策略性地结合了没食子酸（GA）和环状二肽（CDP）的结构和功能特性，合成了能够有效靶向 AD 中铁死亡和淀粉样蛋白毒性的混合分子。这种创新方法标志着传统治疗策略的范式转变。这是第一份关于合成小分子 () 的报告，该小分子可有效对抗铁死亡，同时恢复酶活性并增强其主调节因子 GPX4 的细胞水平。此外，还可破坏 Fe 诱导的 tau 蛋白 LLPS，并有助于减弱异常
• Anti-biofilm and anti-adherence properties of novel cyclic dipeptides against oral pathogens
  作者：Gaëlle Simon、Christopher Bérubé、Normand Voyer、Daniel Grenier

  DOI：10.1016/j.bmc.2018.11.042

  日期：2019.6

  Microorganisms embedded in a biofilm are significantly more resistant to antimicrobial agents and the defences of the human immune system, than their planktonic counterpart. Consequently, compounds that can inhibit biofilm formation are of great interest for novel therapeutics. In this study, a screening approach was used to identify novel cyclic dipeptides that have anti-biofilm activity against oral pathogens. Five new active compounds were identified that prevent biofilm formation by the cariogenic bacterium Streptococcus mutans and the pathogenic fungus Candida albicans. These compounds also inhibit the adherence of microorganisms to a hydroxylapatite surface. Further investigations were conducted on these compounds to establish the structure-activity relationship, and it was deduced that the common cleft pattern is required for these molecules to act effectively against biofilms.